The candidate is currently an Associate Investigator of the Veterans Administration Medical Center West Los Angeles. He has completed his clinical training in internal medicine and nephrology and has worked in the Renal Laboratory for the past three years as a research fellow and as an Associate Investigator. He has a long-standing interest in the biochemical basis of renal function. The Clinical Investigator Award would permit him to continue his work on the regulation of renal ammonia production, and would greatly assist him in his pursuit of a career in academic medicine. Ammonia production and excretion by the kidney play key roles in the maintenance of acid-base homeostasis. Yet little is known about the regulation of ammonia production by functionally active, specific portions of the nephron. A method for examining total ammonia production by isolated, perfused nephron segments was developed by the candidate in an effort to approximate the physiologic state. Results of research to date indicate that total ammonia production is enhanced by perfusion of the tubular lumen and by increased perfusion flow rates. In addition, metabolic acidosis and potassium depletion in vivo have been found to enhance ammonia production by isolated perfused proximal tubules. These studies will be expanded to examine ammonia production by other portions of the nephron. Further experiments are planned to study the influence of altered pH, potassium concentration, calcium concentration, and prostaglandins on ammonia production by specific portions of the nephron perfused in vitro. The proposed research represents a new approach for examining total ammonia production by defined, functionally active portions of the nephron and will provide information previously unobtainable by any other means. Over the past decade, the Renal Laboratory at VAMC West Los Angeles has been a major center for the study of the biochemistry of defined nephron segments. The laboratory is equipped for the efficient performance of tubule perfusion and microanalytical assays.